Sodium picosulfate/magnesium citrate versus 4L split-dose polyethylene glycol for bowel cleansing prior to colonoscopy in high fibre diet African patients.

INTRODUCTION: an adequate bowel preparation is essential for good mucosal inspection during colonoscopy. This study aims to compare the efficacy of two validated oral lavage solutions for colonoscopy preparation in African patients. METHODS: a prospective observational study of patients undergoing colonoscopy in a referral endoscopy facility in Port Harcourt, Nigeria, using sodium picosulfate magnesium citrate (SPMC) and 4L split-dose polyethylene glycol (PEG). Variables collated were sociodemographic, primary indication, comorbidities, Aronchick bowel preparation scale, polyp/adenoma detection, caecal intubation and outcome. Statistical analysis was performed using IBM SPSS version 20. RESULTS: one hundred and twenty-four patients received PEG prior to colonoscopy and SPMC in 175 patients. The age range was from 22 to 92 years; mean age of 53.8 ± 14.2 years for PEG group and 55.3 ± 13.2 years for SPMC group (p=0.361). There were 215 males and 84 females. An excellent/good bowel preparation scale was recorded in 77 (62%) PEG group and 130 (74.3%) for SPMC group (p=0.592). PEG was predominantly used in the early years of endoscopists practice with the odds ratio (OR) of no polyp detection in the PEG vs SPMC groups as 1.64 (confidence interval CI 1.06-2.55) versus 0.76 (CI 0.62-0.92), respectively (p=0.016). For no adenoma detection, OR was 4.18 (CI 1.12-15.60) versus OR 0.63 (CI 0.52-0.75), respectively (p=0.012). CONCLUSION: there is similar efficacy profile using either split volume PEG or SPMC prior to colonoscopy in these African patients. Polyp and adenoma detection rates are highly dependent on the expertise of the endoscopist.

Efficacy and Safety of Regional Anticoagulation with 4% Trisodium Citrate Versus Heparin in Extended Hemodialysis among Critical Patients with Cancer and Acute Kidney Injury.

INTRODUCTION: Patients with cancer admitted to critical care units are at increased risk of being affected with acute kidney injury (AKI) and mortality. Sustained low-efficiency dialysis (SLED) combines the cardiovascular stability of continuous therapy with the operational facility of conventional hemodialysis (HD). Citrate has become an alternative to heparin in anticoagulation because it favors the maintenance of filter patency and reduces bleeding. We analyzed the efficacy and safety of citrate versus heparin use in extended HD for patients with cancer and AKI. METHODS: This retrospective cohort study evaluated patients with cancer and dialytic AKI who received SLED with anticoagulation using citrate versus heparin from January 2014 to June 2017. After stratifying patients by the type of anticoagulation received, we evaluated demographic and clinical data, plus SLED session characteristics. We also analyzed dialysis outcomes, including insufficient session time, hypotension, poor catheter flow, line inversion, and dialysis system coagulation. RESULTS: We identified 423 SLED sessions among 124 patients (41 patients in the heparin group and 83 patients in the citrate group). More sessions with citrate (26.6 vs. 40.9%, p < 0.001) had serum platelet concentrations <50,000/mm3 or <100,000/m3 and ionic calcium (Ca++) values <1.16 mmol/L (33.2 vs. 18.5%, p < 0.001). Dialysis intercurrence occurred in 27% of sessions. The highest odds were associated with heparin sessions (OR 2.88). Compared with the citrate group, the heparin group was subject to more dialysis system coagulation (12.3%), the need for line reversal (9.8%), and insufficient session time (23.9%). CONCLUSION: Citrate represents a safe and effective anticoagulant for SLED for cancer patients with AKI undergoing treatment in the intensive care unit.

Caffeine for preterm infants: Fixed standard dose, adjustments for age or high dose?

Caffeine is an effective treatment for apnea of prematurity and has several important benefits, including decreasing respiratory morbidity and motor impairment. In this article, we focus on the dose of caffeine. We review the evidence regarding the efficacy and safety of standard caffeine dosing and alternative dosing approaches, including the use of high dose caffeine and routine dose adjustments for age. Current evidence suggests high dose caffeine may provide additional benefit in reducing the risk of bronchopulmonary dysplasia and extubation failure, but may also increase the risk of cerebellar hemorrhage and seizures. Increasing the standard caffeine citrate dose every 1-2 weeks to a goal dose of 8 mg per kilogram every 24 h may help maintain therapeutic effect. We conclude by highlighting the need for additional trials before high dose caffeine is routinely used.

Microglia-Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury.

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia-astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

The ligand exchange of citrates to thioabiraterone on gold nanoparticles for prostate cancer therapy.

Cancer is one of the leading causes of morbidity and mortality worldwide and nanotechnology has a significant potential to enhance the therapeutic and diagnostic performance of anti-cancer agents. Our work offers a simple and feasible strategy for thiocompound nanomedicines to be used in cancer therapy. Novel gold nanoparticles conjugated with thioabiraterone (AuNP-S-AB) were synthesized and significant new analytical methodologies were developed for their characterization by UV-Vis, TEM, IR, NMR and TGA. Our synthetic approach was based on the ligand exchange of citrates to thioabiraterone on gold nanoparticles. The average particle size of AuNP-S-AB was 14.5 nm with a spherical shape. The identity of thioabiraterone on the gold nanoparticles was proved by NMR and IR spectroscopy. The coverage of the gold nanoparticles with 40.9% (m/m) thioabiraterone was calculated from a TGA analysis. Molecular interactions between the thiol group of thioabiraterone and gold nanoparticles were evaluated through a combined experimental and theoretical study using the density functional theory (DFT). Additionally, an experiment conducted on hepatocytes or human prostate epithelial cells proved that newly synthesized thiol forms of abiraterone, as well as AuNP-S-AB, are more biocompatible than abiraterone. Our proposed idea of delivering abiraterone with our newly designed AuNP-S-AB may constitute a promising and novel prospect in cancer therapy.

A Randomized Trial Comparing the Bowel Cleansing Efficacy of Sodium Picosulfate/Magnesium Citrate and Polyethylene Glycol/Bisacodyl (The Bowklean Study).

Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject's treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.

Participation of CXCL1 in the glial cells during neuropathic pain.

Neuropathic pain is a chronic pain characterized by injury to the central or peripheral nervous system and that most often causes disability in individuals. Among the mechanisms involved in central sensitization during neuropathic pain are cytokines and chemokines released by spinal glial cells; however, these mechanisms are not well elucidated. Thus, the present study aimed to investigate the involvement of Chemokine (C-X-C motif) ligand 1 (CXCL1) and glial cells in this process. Male Wistar rats weighing 220-240 g were used and underwent a neuropathic pain model induced by chronic constriction injury (CCI). To investigate the involvement of CXCL1, chemokine receptor type 2 (CXCR2), mitogen-activated protein kinases (MAPK) p38, and microglia and astrocytes, the following drugs were used: SB225002, an CXCR2 antagonist; SML0543, a MAPK p38 inhibitor; minocycline, a microglia inhibitor; fluorocitrate, an astrocytes inhibitor; and recombinant CXCL1. The microglia, astrocytes, CXCL1, and MAPK p38 protein levels was evaluated by a Western blot assay. Furthermore, an immunofluorescence assay was performed to localize microglia and astrocytes immunoreactivity in the spinal cord. The results demonstrated that both CCI and CXCL1 induced nociception, and this effect was reversed by SB225002. In addition, minocycline, fluorocitrate, and SML0543 reversed the mechanical allodynia induced by CCI. Furthermore, there was an increase of spinal CXCL1 and microglial marker Iba1 protein levels , which was reversed by SB225002. This antagonist also reduced the Iba1 immunoreactivity in spinal cord. Thus, the present study suggests that the CXCL1 chemokine participates in neuropathic pain through CXCR2 activation in spinal microglia.

Accuracy of Oral 67Gallium Citrate Scintigraphy in assessment of inflammatory activity of Crohn's disease.

AIM: The main goal in Crohn´s disease (CD) is a sustained suppression of inflammatory activity associated with mucosa healing in endoscopic evaluation. During clinical routine, there are small numbers of good markers to monitor inflammatory activity under treatment. We postulated that Oral 67Gallium Citrate Scintigraphy is able to mark inflammatory disease in mucosa and deep inflammation in CD, when used in oral form. OBJECTIVE: Measure the accuracy of Oral 67Gallium Citrate Scintigraphy in intestinal inflammatory activity of Crohn´s disease. PATIENTS AND METHODS: In a prospective consecutive cross-sectional study from January 2018 to June 2019, the ileocolonic region of 32 patients with CD were studied by dividing into four regions of interest (ROI) from the ileum to the rectum. A total of 128 intestinal segments were analyzed in cluster data. Accuracy values of Oral 67Gallium Scintigraphy and colonoscopy tests were evaluated with the histological reference test. Values of the respective receiver operating characteristic (ROC) curves were obtained  and compared. The reliability between the tests was evaluated by Kappa statistical with the segment-level analyses using variance adjustments. All statistical analyses were performed with a test significance level of 0.05. RESULTS: The study population included 32 patients with CD (10 men, 22 women; average age 39 years). Disease time was five years on average. Anti-TNFs treatment was found in 71%. The most found phenotype of the Montreal classification was L3. Differences in ROC curves for colonoscopy (0.94) and Oral 67Ga Scintigraphy (0.96) did not show significant value (p = 0.32). The sensitivity of scintigraphy to detect intestinal inflammatory activity in CD was 64%, specificity of 96% and accuracy of 84%. A high agreement was found between oral scintigraphy and histological measurements with kappa = 0.64. CONCLUSIONS: Oral 67Ga Scintigraphy had similar accuracy and agreement compared to colonoscopy in the identification of inflammatory activity in Crohn´s Disease. This new approach may be useful and less invasive for long term follow-ups.

[Optimal Laxatives for Oral Colonoscopy Bowel Preparation: from High-volume to Novel Low-volume Solutions].

Optimal bowel preparation is essential for a more accurate, comfortable, and safe colonoscopy. The majority of postcolonoscopy colorectal cancers can be explained by procedural factors, mainly missed polyps or inadequate examination. Therefore the most important goal of optimal bowel preparation is to reduce the incidence of colorectal cancer. Although adequate preparation should be achieved in 85-90% or more of all colonoscopy as a quality indicator, unfortunately 20-30% shows inadequate preparation. Laxatives for oral colonoscopy bowel preparation can be classified into polyethylene glycol (PEG)-electrolyte lavage solution, osmotic laxatives, stimulant laxatives, and divided into high-volume solution (≥3 L) and low-volume solution (<3 L). The updated 2019 European Society of Gastrointestinal Endoscopy (ESGE) guideline is broadly similar to the 2014 American Society for Gastrointestinal Endoscopy (ASGE) recommendations and reaffirms the importance of split-dosing. However, new ESGE guideline, unlike the 2014 ASGE recommendation, suggests the use of high volume or low volume PEG-based regimens as well as that of non-PEG based agents that have been clinically validated for most outpatient scenarios. For effective, safe, and highly adherent bowel preparation, physicians who prescribe and implement colonoscopy should properly know the advantages and limitations, the dosing, and the timing of regimens. Recently many studies have attempted to find the most ideal regimens, and more convenient, effective, and safe regimens have been developed by reducing the dosing volume and improving the taste. The high tolerability and acceptability of the new low-volume regimens suggest us how we should use it to increase the participation of the national colorectal cancer screening program.

Influence of prevention of caffeine citrate on cytokine profile and bronchopulmonary dysplasia in preterm infants with apnea.

BACKGROUND: This study aims to investigate the preventive effects of caffeine citrate on cytokine profile and bronchopulmonary dysplasia (BPD) in preterm infants with apnea. METHODS: Preterm infants with apnea who were born at less than 32 weeks of gestational age and birth weight ≤1500 g were randomly divided into caffeine citrate prevention group and caffeine citrate treatment group. Preterm infants in caffeine citrate prevention group who were at risk of developing recurrent apnea were given to caffeine citrate within 8 h after birth. Those in caffeine citrate treatment group experienced apnea after birth were given to caffeine citrate for treatment. Preterm infants in both groups were treated with the same respiratory management and other conventional therapy. After drug discontinuation, levels of cytokine profile, and incidence of BPD were compared between two groups. RESULTS: A total of 56 preterm infants were enrolled. Differences in gestational age (P=0.11) and birth weight (P=0.251) were not statistically significant. Differences in application time of caffeine citrate (P=0.356), hour of ventilator use (P=0.152), length of stay (P=0.416) and BPD morbidity (P=1.00) between two groups were not statistically significant. At birth, there were no statistically significant in levels of IL-6 (P=0.063) and IL-8 (P=0.125) between two groups. After conventional therapy, levels of IL-6 (P=0.001) and IL-8 (P=0.001) significantly decreased in caffeine citrate prevention group compared with those in caffeine citrate treatment group. CONCLUSIONS: Prevention usage of caffeine citrate in preterm infants with apnea could reduce the level of cytokine profile and the incidence of BPD.

The quality of colonoscopy preparation in a private clinical practice setting.

No data are available on the quality of the preparation for colonoscopy in private medicine in Spain. We report a retrospective study of the efficacy and tolerability of bowel preparation in the standard clinical practice in a private center.

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. METHODS: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. RESULTS: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.

Caffeine citrate enhanced cisplatin antitumor effects in osteosarcoma and fibrosarcoma in vitro and in vivo.

BACKGROUND: While multiagent chemotherapy has dramatically improved the prognosis of sarcoma, the novel chemotherapeutics have hardly developed over the past 30 years. Caffeine can induce apoptosis, delays in cell cycle progression and can enhance the cytocidal effects of anti-cancer agents. Citrate has been reported to enhance the cytocidal effect of cisplatin in gastric cancer in vitro. However its effect in sarcoma cells had not been reported. METHODS: This study was designed to evaluate whether the addition of caffeine, citrate, or caffeine citrate to cisplatin improved its cytocidal effect (cell survival, proliferation, and apoptosis) on human osteosarcoma (HOS), human fibrosarcoma (HT1080) and murine osteosarcoma (LM8) cell lines. We also tested the various combinations in a mouse heterotopic transplantation model in vivo. In cell survival assay, combination index (CI) of caffeine citrate was calculated as a combination of anhydrous caffeine and citric acid, and the synergy was evaluated (CI < 1.0). RESULTS: In all cell lines, cisplatin combined with caffeine citrate significantly reinforced the anticancer effect compared with cisplatin alone, combination of cisplatin and anhydrous caffeine, and combination of cisplatin and citric acid. Moreover, CI was < 1.0 in all conditions. The anticancer agent reinforcement effect of caffeine citrate was synergy of anhydrous caffeine and citric acid. In cell proliferation and cell cycle assay revealed that caffeine citrate had most strong effect as a combination drug than caffeine and citric acid in inducing G0/G1 cell-cycle arrest with subsequent suppressed cell proliferation. In mitochondrial depolarization and caspase 3/7 activity assay revealed that caffeine citrate had most strong effect as a combination drug than caffeine and citric acid in apoptosis associated with decreased mitochondrial membrane potential. In vivo, three different drug concentrations were tested, and cisplatin combined with caffeine citrate was found to have the strongest antitumor effect. CONCLUSIONS: This is the first report demonstrating that caffeine citrate has a significantly greater potentiating effect on cisplatin than adding either caffeine or citric acid. The combination of cisplatin with caffeine citrate is a novel treatment that might hold promise for improving the outcome of osteosarcoma and fibrosarcoma, which up till now has generally not responded well to chemotherapy.

Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants.

OBJECTIVE: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. STUDY DESIGN: We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. RESULTS: Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. CONCLUSIONS: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

The impact of low- versus standard-volume bowel preparation on participation in primary screening colonoscopy: a randomized health services study.

BACKGROUND: The aim of this study was to evaluate the impact of low-volume vs. standard-volume bowel preparation on participation in screening colonoscopy, bowel preparation quality, and lesion detection rates. METHODS: This was a multicenter, randomized, health services study within the population-based primary colonoscopy screening program in Poland. Individuals aged 55 - 62 years were randomized in a 1:1 ratio to bowel preparation with a low-volume (0.3 L sodium picosulfate with magnesium citrate) or standard-volume (4 L polyethylene glycol) regimen and then invited to participate in screening colonoscopy. The primary outcome measure was the rate of participation in screening colonoscopy. Compliance with the assigned bowel preparation, bowel preparation quality, and lesion detection rates were also evaluated. RESULTS: A total of 13 621 individuals were randomized and 13 497 were analyzed (6752 in the low-volume group and 6745 in the standard-volume group). The participation rate (16.6 % vs. 15.5 %; P = 0.08) and compliance rate (93.3 % vs. 94.1 %; P = 0.39) did not differ significantly between the groups. In the low-volume group, fewer participants had adequate bowel preparation compared with the standard-volume group (whole colon 79.0 % vs. 86.4 %, P < 0.001; proximal colon 80.1 % vs. 87.3 %, P < 0.001). Detection rates of advanced adenoma (AADR) and advanced serrated polyps (ASPDR) were lower in the low-volume group than in the standard-volume group (AADR in the proximal colon 2.6 % vs. 4.3 %, P = 0.02; ASPDR in the whole colon 2.0 % vs. 3.3 %, P = 0.04; ASPDR in the proximal colon 1.0 % vs. 1.9 %, P = 0.048). CONCLUSION: When compared with a standard-volume bowel preparation with polyethylene glycol, low-volume bowel preparation with sodium picosulfate/magnesium citrate did not improve participation rate or lesion detection rates, and negatively affected bowel preparation quality.

Targeting iron metabolism in high-grade glioma with 68Ga-citrate PET/MR.

Noninvasive tools that target tumor cells could improve the management of glioma. Cancer generally has a high demand for Fe(III), an essential nutrient for a variety of biochemical processes. We tested whether 68Ga-citrate, an Fe(III) biomimetic that binds to apo-transferrin in blood, detects glioma in preclinical models and patients using hybrid PET/MRI. Mouse PET/CT studies showed that 68Ga-citrate accumulates in subcutaneous U87MG xenografts in a transferrin receptor-dependent fashion within 4 hours after injection. Seventeen patients with WHO grade III or IV glioma received 3.7-10.2 mCi 68Ga-citrate and were imaged with PET/MR 123-307 minutes after injection to establish that the radiotracer can localize to human tumors. Multiple contrast-enhancing lesions were PET avid, and tumor to adjacent normal white matter ratios were consistently greater than 10:1. Several contrast-enhancing lesions were not PET avid. One minimally enhancing lesion and another tumor with significantly reduced enhancement following bevacizumab therapy were PET avid. Advanced MR imaging analysis of one patient with contrast-enhancing glioblastoma showed that metabolic hallmarks of viable tumor spatially overlaid with 68Ga-citrate accumulation. These early data underscore that high-grade glioma may be detectable with a radiotracer that targets Fe(III) transport.

Comparative safety of bowel cleansers: protocol for a systematic review and network meta-analysis.

INTRODUCTION: The US Food and Drug Administration has withdrawn the bowel cleansing kit HalfLytely (PEG 3500) with 10 mg bisacodyl tablets due to an increased risk of ischaemic colitis compared with the same kit with only 5 mg bisacodyl. This is of interest in Canada given that the bowel cleansing kit Bi-Peglyte (PEG 3500) with 15 mg bisacodyl is currently approved for use. The objective is to assess the comparative safety of various bowel cleansers with or without bisacodyl, with a primary interest inpolyethylene glycol (PEG)-based and sodium-picosulfate-based products. METHODS AND ANALYSIS: Given the existing volume of the literature, the review will be conducted in two stages. Stage 1 will consist of a scoping exercise by searching MEDLINE, Embase and the Cochrane Library (up to 21 November 2017) to identify randomised controlled trials, quasirandomised studies and non-randomised studies in which any bowel cleanser regimens were compared among persons undergoing colonoscopy. The outcomes will be mapped to establish a listing of the studies and their comparisons and outcomes currently available in the literature. From this, a data synthesis plan will be determined. In stage 2, a systematic review with meta-analyses will be pursued, focused on the bowel cleanser comparisons and outcomes of interest identified in stage 1. Two reviewers will screen, extract and quality assess the articles. Outcomes of interest include ischaemic colitis, electrolyte imbalances and their consequences, seizures, bowel perforation and patient tolerability. If sufficient data exist and studies are of sufficient homogeneity, network meta-analyses (NMAs) will be performed. ETHICS AND DISSEMINATION: Ethics approval was not necessary due to study design. Updating the safety profile of bowel cleansers among the generally healthy population undergoing colonoscopy is pertinent given recent approval changes. This will be the first NMA within this population. Policy considerations may be reconsidered to minimise risk during bowel cleanser use. PROSPERO REGISTRATION NUMBER: CRD42018084720.